114802-07-2Relevant academic research and scientific papers
Anacardic acid derivatives as inhibitors of glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma cruzi
Pereira, Junia M.,Severino, Richele P.,Vieira, Paulo C.,Fernandes, Joao B.,da Silva, M. Fatima G.F.,Zottis, Aderson,Andricopulo, Adriano D.,Oliva, Glaucius,Correa, Arlene G.
, p. 8889 - 8895 (2008/12/23)
Chagas' disease, a parasitic infection caused by the flagellate protozoan Trypanosoma cruzi, is a major public health problem affecting millions of individuals in Latin America. On the basis of the essential role in the life cycle of T. cruzi, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been considered an attractive target for the development of novel antitrypanosomatid agents. In the present work, we describe the inhibitory effects of a small library of natural and synthetic anacardic acid derivatives against the target enzyme. The most potent inhibitors, 6-n-pentadecyl- (1) and 6-n-dodecylsalicilic acids (10e), have IC50 values of 28 and 55 μM, respectively. The inhibition was not reversed or prevented by the addition of Triton X-100, indicating that aggregate-based inhibition did not occur. In addition, detailed mechanistic characterization of the effects of these compounds on the T. cruzi GAPDH-catalyzed reaction showed clear noncompetitive inhibition with respect to both substrate and cofactor.
